The two leading causes of untreatable blindness in the developed world are retinitis pigmentosa (RP) and end-stage macular degeneration (AMD). While the etiology of the diseases varies, they share a common outcome, the degeneration of photoreceptors, the light sensing cells of the retina. One approach to restoring visual function is to stimulate the remaining retinal circuitry using a retinal prosthetic that encodes the visual information into electrical signals. The challenge is to design such a system that interfaces with the diseased retina and provides a high resolution representation of the visual environment. This project brings together a unique combination of engineers, neurobiologists, and ophthalmologists to complete the development and evaluation of a high-resolution retinal prosthetic system designed specifically to achieve functional levels of vision. In this system the processed images of the visual scene are projected by pulsed infrared light onto a subretinally placed microphotodiode array. Photovoltaic pixels in the array convert pulsed light into biphasic pulses of electric current that directly stimulate retinal neurons. This Optoelectronic Retinal Prosthetic System offers several novel and advantageous features: hundreds or thousands of pixels in the implant can be activated simultaneously and independently, simplified surgical procedure, user-adjustable image processing, high resolution stimulation, a natural link between eye movements and image perception, a 3- dimensional implant structure that facilitates close proximity of neurons with stimulating electrodes, and modular design of the implant that allows for expansion of the stimulated field. Such a versatile system could be used to address the divergent needs of RP and AMD patients. Most of the system components have been developed and some aspects tested. Prototype photodiode arrays show long-term biocompatibility, and provide retinal stimulation upon illumination with IR flash. This proposal represents the final two stages of system development in rat and cat models of RP, prior to clinical trials. The proposed experiments will assess: stimulation efficacy and safety limits, long term biocompatibility, and limits of spatial resolution with flat and 3-dimensional implants in electrophysiological and behavioral experiments. PUBLIC HEALTH RELEVANCE: The two leading causes of untreatable blindness in the developed world are retinitis pigmentosa (RP) and end-stage age-related macular degeneration (AMD). Both diseases result in the loss of photoreceptors, while most of the signal processing neurons in the retina are preserved. We propose to restore sight of the blind by delivering visual information to the remaining cells in the neural retina using high resolution electrical stimulation by a photovoltaic subretinal prosthesis. This optoelectronic system represents an innovative and versatile design that addresses the divergent needs of patients with both RP and AMD.